(3R*,4S*)-7-hydroxymethyl-2,2,9-trimethyl-4-(phenethylamino)-3,4-dihydro-2H-pyrano[2,3-g]quinolin-3-ol (compound (3)) has an anti-arrhythmic action, and its possible use as a pharmaceutical product has been known (e.g., see Patent Document 1).

As a method for synthesizing the compound (3), a method is known in which 2,2,7,9-tetramethyl-2H-pyrano[2,3-g]quinoline (compound (1)) is reacted with m-chloroperbenzoic acid, followed by a reaction with acetic anhydride to obtain (2,2,9-trimethyl-2H-pyrano[2,3-g]quinolin-7-yl)-methyl acetate (compound (6)), as shown in the following reaction formula (I), and the compound (6) is transferred to the compound (3). In a reaction of the reaction formula (I), it is presumed that the compound (1) is oxidized by m-chloroperbenzoic acid to produce 2,2,7,9-tetramethyl-2H-pyrano[2,3-g]quinoline 6-oxide (compound (2)) in which the nitrogen atom in the quinoline ring is N-oxidized. However, the details of the reaction were not clear.
In the production method through the reaction formula (I), m-chloroperbenzoic acid is used as an oxidizing agent. m-Chloroperbenzoic acid is a hazardous reagent, which is classified as Class 5.2 (organic peroxides) of the UN Recommendations on the Transport of Dangerous Goods, and care is necessary in use on an industrial scale.
Therefore, in order to establish a method for industrially producing the compound (3), the establishment of a method for producing the compound (2), in particular, a method that enables safe, large-volume production without a hazardous reagent such as m-chloroperbenzoic acid has been required.

For synthesis of a N-oxide compound such as a pyridine ring and a quinoline ring that are generally a nitrogen-containing heterocycle, an oxidation process using peracetic acid (e.g., see Non-Patent Document 1), and an oxidation process using rare metal or heavy metal as a catalyst and hydrogen peroxide (e.g., see Non-Patent Documents 2 and 3) are known. However, the processes have a problem in safety of an oxidizing agent.
As a safe oxidizing agent capable of causing an N-oxidation reaction, OXONE (registered trademark by DuPont Co.) is known. OXONE is a white crystal that is a double salt of potassium hydrogen persulfate-potassium hydrogen sulfate-potassium sulfate, and is an excellent oxidizing agent that is industrially handled with ease. As an N-oxidation reaction using OXONE, a reaction method using only OXONE is known. However, the yield in this reaction is very low (see, Non-Patent Document 4). As another example of the N-oxidation reaction using OXONE, a method of improving the reactivity by addition of a base is known. However, the details of this reaction are not clear, and in particular, a method of using the base and an effect thereof are not established, for example, the equivalent weight of base to be used is excessive or insufficient for OXONE (e.g., see Non-Patent Documents 5 and 6). As further another example of the N-oxidation reaction using OXONE, a method of improving the reactivity by further addition of acetone is also known (e.g., see Non-Patent Document 7). However, dimethyl dioxirane that is a hazardous peroxide is considered to be produced during this reaction, and therefore this method has a problem of unsuitability as an industrial production method.